Influenza infection (also referred to as “influenza” or “the flu”) is one of the most common diseases known to man causing between three and five million cases of severe illness and between 250,000 and 500,000 deaths every year around the world. Influenza rapidly spreads in seasonal epidemics affecting 5 to 15% of the population and the burden on health care costs and lost productivity are extensive (World Healthcare Organization (WHO)). There are three types of influenza flu virus (types A, B and C) responsible for infectious pathologies in humans and animals. Currently, the type A and type B viruses are the agents responsible for the influenza epidemics and pandemics observed in humans.
Current approaches to dealing with annual influenza epidemics include annual vaccination, preferably generating heterotypic cross-protection. However, circulating influenza viruses in humans are subject to permanent antigenic changes which require annual adaptation of the influenza vaccine formulation to ensure the closest possible match between the influenza vaccine strains and the circulating influenza strains. Alternatively, antiviral drugs, such as oseltamivir (TAMIFLU®) can be effective for prevention and treatment of influenza infection. The number of influenza virus strains showing resistance against antiviral drugs such as oseltamivir is, however, increasing.
An alternative approach is the development of antibody-based prophylactic or therapeutic means to neutralize various seasonal influenza viruses.
Broadly cross-neutralizing antibodies recognizing epitopes in the conserved stem-region of HA of influenza A viruses of phylogenetic group 1 (such as influenza viruses comprising HA of the H1 or H5 subtype) have recently been disclosed (e.g., CR6261, see WO2008/028946), as well as cross-neutralizing antibodies recognizing a highly conserved epitope in the stem-region of HA of influenza A viruses of phylogenetic group 2, such as influenza viruses comprising HA of the H3 and/or H7 subtypes (e.g., CR8020, CR8043; see WO 2010/130636). More recently, antibodies capable of binding to and neutralizing influenza A viruses of both phylogenetic group 1 and group 2, as well as influenza B viruses were discovered (e.g., CR9114, described in application no. EP11173953.8).
To date, less attention has been paid to influenza B viruses. This may be due to the fact that—primarily being restricted to humans as host—influenza B viruses lack the large animal reservoirs that key to the emergence of pandemic influenza A strains. However, the cumulative impact of annual epidemics during interpandemic periods exceeds that of pandemics and although the morbidity and mortality rates attributable to influenza B are lower than those of e.g., H3N2 viruses, they are higher than those of H1N1 viruses (Thompson (2003), Thompson (2004)).
The evolution of influenza B viruses is characterized by co-circulation of antigenically and genetically distinct lineages for extended periods of time. Two lineages, represented by the prototype viruses B/Victoria/2/87 (Victoria lineage) and B/Yamagata/16/88 (Yamagata lineage), are currently distinguished (Kanegae (1990), Rota (1990)). B/Yamagata was the major lineage circulating until the 1980s, when B/Victoria lineage viruses appeared. Since then, drift variants of both influenza B lineages have been co-circulating globally, with both lineages concurrently circulating in recent influenza seasons.